{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:44:10Z","timestamp":1790491450234,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP-2019\/67"],"award-info":[{"award-number":["RSP-2019\/67"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Commiphora myrrh resin (Myrrh) has been used in traditional Arabic medicine to treat various inflammatory diseases. Two furano-sesquiterpenoids, 2-methoxyfuranodiene (CM1) and 2-acetoxyfuranodiene (CM2), were isolated from the chloroform fraction of the ethanolic extract of Arabic Commiphora myrrh resin. The cytotoxicity of the compounds was evaluated using human liver carcinoma, breast cancer cells (HepG2 and MCF-7, respectively) and normal human umbilical vein endothelial cells (HUVECs) cell lines. The development toxicity and anti-angiogenic activity of both compounds were also evaluated using zebrafish embryos. Cell survival assays demonstrated that both compounds were highly cytotoxic in HepG2 and MCF7 cells, with IC50 values of 3.6 and 4.4 \u00b5M, respectively. Both compounds induced apoptosis and caused cell cycle arrest in treated HepG2 cells, which was observed using flow cytometric analysis. The development toxicity in zebrafish embryos showed the chronic toxicity of both compounds. The toxicity was only seen when the embryos remained exposed to the compounds for more than three days. The compound CM2 showed a significant level of anti-angiogenic activity in transgenic zebrafish embryos at sublethal doses. Thus, we demonstrated the cytotoxic properties of both compounds, suggesting that the molecular mechanism of these compounds should be further assessed.<\/jats:p>","DOI":"10.3390\/molecules25061318","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T07:29:07Z","timestamp":1584689347000},"page":"1318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Cytotoxic Evaluation and Anti-Angiogenic Effects of Two Furano-Sesquiterpenoids from Commiphora myrrh Resin"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1034-7441","authenticated-orcid":false,"given":"Ali","family":"S. Alqahtani","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Medication Safety Research Chair, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-7822","authenticated-orcid":false,"given":"Fahd A.","family":"Nasr","sequence":"additional","affiliation":[{"name":"Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-6381","authenticated-orcid":false,"given":"Omar M.","family":"Noman","sequence":"additional","affiliation":[{"name":"Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-2443","authenticated-orcid":false,"given":"Muhammad","family":"Farooq","sequence":"additional","affiliation":[{"name":"Bioproducts Research Chair, College of Science, Department of Zoology, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Alhawassi","sequence":"additional","affiliation":[{"name":"Medication Safety Research Chair, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajhul","family":"Qamar","sequence":"additional","affiliation":[{"name":"Central Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"El-Gamal","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lichota, A., and Gwozdzinski, K. (2018). Anticancer activity of natural compounds from plant and marine environment. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113533"},{"key":"ref_3","first-page":"347","article-title":"Gum guggul: An Ayurvedic boom","volume":"6","author":"Poonia","year":"2014","journal-title":"Int. J. Pharmacogn Phytochem Res."},{"key":"ref_4","first-page":"731","article-title":"Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity: A biochemical and histopathological evaluation","volume":"32","author":"Ojha","year":"2011","journal-title":"J. Environ. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gebrehiwot, M., Asres, K., Bisrat, D., Mazumder, A., Lindemann, P., and Bucar, F. (2015). Evaluation of the wound healing property of Commiphora guidottii Chiov. Ex. Guid. BMC Complement. Altern Med., 15.","DOI":"10.1186\/s12906-015-0813-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.jsps.2016.10.011","article-title":"Analysis of inorganic and organic constituents of myrrh resin by GC-MS and ICP-MS: An emphasis on medicinal assets","volume":"25","author":"Ahamad","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.biopha.2018.06.171","article-title":"Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2\/ARE\/HO-1 signaling","volume":"106","author":"Mahmoud","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12936-019-2752-8","article-title":"In vitro and in vivo studies on anti-malarial activity of Commiphora africana and Dichrostachys cinerea used by the Maasai in Arusha region, Tanzania","volume":"18","author":"Kweyamba","year":"2019","journal-title":"Malar. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jep.2012.05.025","article-title":"The genus Commiphora: A review of its traditional uses, phytochemistry and pharmacology","volume":"142","author":"Shen","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8497980","DOI":"10.1155\/2019\/8497980","article-title":"Subcutaneous injection of myrrh essential oil in mice: Acute and subacute toxicity study","volume":"2019","author":"Lamichhane","year":"2019","journal-title":"Evid Based Complem. Alternat Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.5935\/1518-0557.20160050","article-title":"Risks of myrrh usage in pregnancy","volume":"20","author":"Kaddour","year":"2016","journal-title":"JBRA Assist. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.2174\/1568026617666170130112109","article-title":"The use of the zebrafish model to aid in drug discovery and target validation","volume":"17","author":"Yoganantharjah","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3389\/fnins.2018.00976","article-title":"The utility of zebrafish as a model for screening developmental neurotoxicity","volume":"12","author":"Giordani","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1254\/fpj.154.78","article-title":"Next generation zebrafish-based drug discovery and precision medicine","volume":"154","author":"Tanaka","year":"2019","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/0031-9422(83)80223-4","article-title":"Furanosesquiterpenes from the essential oil of myrrh","volume":"22","author":"Noble","year":"1983","journal-title":"Phytochemistry"},{"key":"ref_16","first-page":"763","article-title":"An update review on Commiphora molmol and related species","volume":"38","author":"Tonkal","year":"2008","journal-title":"J. Egypt. Soc. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.30750\/ijpbr.3.3.2","article-title":"Evaluation of antibacterial activity of Commiphora myrrha against antibiotic resistant clinical pathogens","volume":"3","author":"Shaik","year":"2015","journal-title":"IJPBR"},{"key":"ref_18","unstructured":"Tao, S., and Hong-xiang, L. (2008). Chemical constituents from resin of Commiphora species and their biological activities. NPRD, 20."},{"key":"ref_19","first-page":"109","article-title":"Distribution, chemical components and bioactivity of resin herbs: Research advances","volume":"36","author":"Su","year":"2009","journal-title":"IJPR"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/ffj.1193","article-title":"Isolation and characterization of several aromatic sesquiterpenes from Commiphora myrrha","volume":"18","author":"Zhu","year":"2003","journal-title":"Flavour Fragr. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/0031-9422(82)83164-6","article-title":"Furanosesquiterpenoids of Commiphora erythraea and C. myrrh","volume":"21","author":"Maradufu","year":"1982","journal-title":"Phytochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1056\/NEJMra0901217","article-title":"Cell death","volume":"361","author":"Hotchkiss","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pfeffer, C.M., and Singh, A.T.K. (2018). Apoptosis: A target for anticancer therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020448"},{"key":"ref_24","first-page":"421","article-title":"Herbal medicine as inducers of apoptosis in cancer treatment","volume":"4","author":"Safarzadeh","year":"2014","journal-title":"Adv. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/B978-0-12-385493-3.00004-8","article-title":"Apoptosis and beyond: Cytometry in studies of programmed cell death","volume":"103","author":"Wlodkowic","year":"2011","journal-title":"Methods Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gabrielli, B., Brooks, K., and Pavey, S. (2012). Defective cell cycle checkpoints as targets for anti-cancer therapies. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00009"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3892\/ol.2013.1520","article-title":"Composition and potential anticancer activities of essential oils obtained from myrrh and frankincense","volume":"6","author":"Chen","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.3892\/or.2015.3725","article-title":"Cycloartan-24-ene-1alpha,2alpha,3beta-triol, a cycloartane-type triterpenoid from the resinous exudates of Commiphora myrrha, induces apoptosis in human prostatic cancer PC-3 cells","volume":"33","author":"Gao","year":"2015","journal-title":"Oncol Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/379029a0","article-title":"Analgesic effects of myrrh","volume":"379","author":"Dolara","year":"1996","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.fitote.2011.02.002","article-title":"Anti-inflammatory, antioxidant and antifungal furanosesquiterpenoids isolated from Commiphora erythraea (Ehrenb)","volume":"82","author":"Fraternale","year":"2011","journal-title":"Engl. Resin. Fitoterapia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1016\/j.bmcl.2013.09.093","article-title":"Anti-cancer evaluation of carboxamides of furano-sesquiterpene carboxylic acids from the soft coral Sinularia kavarattiensis","volume":"23","author":"Rajaram","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s10495-009-0332-z","article-title":"Furano-sesquiterpene from soft coral, Sinularia kavarittiensis: Induces apoptosis via the mitochondrial-mediated caspase-dependent pathway in THP-1, leukemia cell line","volume":"14","author":"Arepalli","year":"2009","journal-title":"Apoptosis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacbts.2017.01.004","article-title":"Using zebrafish for high-throughput screening of novel cardiovascular drugs","volume":"2","author":"Kithcart","year":"2017","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/bs.mcb.2016.10.004","article-title":"Chemical screening in zebrafish for novel biological and therapeutic discovery","volume":"138","author":"Wiley","year":"2017","journal-title":"Methods Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-3-319-30654-4_5","article-title":"Identifying novel cancer therapies using chemical genetics and zebrafish","volume":"916","author":"Dang","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fncel.2019.00425","article-title":"Recessive inheritance of congenital hydrocephalus with other structural brain abnormalities caused by compound heterozygous mutations in ATP1A3","volume":"13","author":"Allocco","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109406","DOI":"10.1016\/j.ecoenv.2019.109406","article-title":"Linking chemical exposure to lipid homeostasis: A municipal waste water treatment plant influent is obesogenic for zebrafish larvae","volume":"182","author":"Barbosa","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12936","DOI":"10.1038\/s41598-019-49217-7","article-title":"Functional analysis of new human Bardet-Biedl syndrome loci specific variants in the zebrafish model","volume":"9","author":"Novas","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00439-019-02055-z","article-title":"Looking to the future of zebrafish as a model to understand the genetic basis of eye disease","volume":"138","author":"Cavodeassi","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129398","DOI":"10.1016\/j.bbagen.2019.07.007","article-title":"Design and biological assessment of membrane-tethering neuroprotective peptides derived from the pituitary adenylate cyclase-activating polypeptide type 1 receptor","volume":"1863","author":"Jamadagni","year":"2019","journal-title":"BBA-Gen. Subj."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Doro, E., Jacobs, S.H., Hammond, F.R., Schipper, H., Pieters, R.P., Carrington, M., Wiegertjes, G.F., and Forlenza, M. (2019). Visualizing trypanosomes in a vertebrate host reveals novel swimming behaviours, adaptations and attachment mechanisms. Elife, 8.","DOI":"10.7554\/eLife.48388"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/CIRCULATIONAHA.119.038376","article-title":"Defects in the exocyst-cilia machinery cause bicuspid aortic valve disease and aortic stenosis","volume":"140","author":"Fulmer","year":"2019","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1089\/thy.2019.0009","article-title":"In vitro characterization of human, mouse, and zebrafish MCT8 orthologues","volume":"29","author":"Groeneweg","year":"2019","journal-title":"Thyroid"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1089\/thy.2019.0122","article-title":"Small-molecule screening in zebrafish embryos identifies signaling pathways regulating early thyroid development","volume":"29","author":"Haerlingen","year":"2019","journal-title":"Thyroid"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.scitotenv.2019.06.028","article-title":"Fish behavior: A promising model for aquatic toxicology research","volume":"686","author":"Hong","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109221","DOI":"10.1016\/j.biopha.2019.109221","article-title":"Ardisia crispa root hexane fraction suppressed angiogenesis in human umbilical vein endothelial cells (HUVECs) and in vivo zebrafish embryo model","volume":"118","year":"2019","journal-title":"Biomed. Pharmacother"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Konantz, M., Schurch, C., Hanns, P., Muller, J.S., Sauteur, L., and Lengerke, C. (2019). Modeling hematopoietic disorders in zebrafish. Dis. Model. Mech., 12.","DOI":"10.1242\/dmm.040360"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bone.2019.02.009","article-title":"Using zebrafish to study skeletal genomics","volume":"126","author":"Kwon","year":"2019","journal-title":"Bone"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lin, Y., Xiang, X., Chen, T., Mao, G., Deng, L., Zeng, L., and Zhang, J. (2019). In vivo monitoring the dynamic process of acute retinal hemorrhage and repair in zebrafish with spectral-domain optical coherence tomography. J. Biophotonics, e201900235.","DOI":"10.1002\/jbio.201900235"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pott, A., Rottbauer, W., and Just, S. (2019). Streamlining drug discovery assays for cardiovascular disease using zebrafish. Expert Opin. Drug Dis., 1\u201311.","DOI":"10.1080\/17460441.2020.1671351"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1016\/j.bbadis.2019.07.009","article-title":"Knocking out lca5 in zebrafish causes cone-rod dystrophy due to impaired outer segment protein trafficking","volume":"1865","author":"Qu","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1089\/zeb.2019.1754","article-title":"Machine learning methods for automated quantification of ventricular dimensions","volume":"16","author":"Schutera","year":"2019","journal-title":"Zebrafish"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"734212","DOI":"10.1016\/j.aquaculture.2019.734212","article-title":"Emerging regulatory mechanisms and functions of autophagy in fish","volume":"511","author":"Xia","year":"2019","journal-title":"Aquaculture"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cao, B., Wei, X.C., Xu, X.R., Zhang, H.Z., Luo, C.H., Feng, B., Xu, R.C., Zhao, S.Y., Du, X.J., and Han, L. (2019). Seeing the unseen of the combination of two natural resins, frankincense and myrrh: Changes in chemical constituents and pharmacological activities. Molecules, 24.","DOI":"10.3390\/molecules24173076"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cbi.2017.04.012","article-title":"Commiphora molmol resin attenuates diethylnitrosamine\/phenobarbital-induced hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis and Nrf2\/ARE\/HO-1 signaling","volume":"270","author":"Mahmoud","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5893","DOI":"10.1158\/0008-5472.CAN-09-0755","article-title":"Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis","volume":"69","author":"Pang","year":"2009","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1002\/ijc.26251","article-title":"Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers","volume":"130","author":"Yadav","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3389\/fphys.2016.00056","article-title":"Zebrafish as an emerging model organism to study angiogenesis in development and regeneration","volume":"7","author":"Chavez","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1023\/A:1026598300052","article-title":"Zebrafish angiogenesis: A new model for drug screening","volume":"3","author":"Serbedzija","year":"1999","journal-title":"Angiogenesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1007\/s13346-019-00641-2","article-title":"Development of anti-angiogenic erlotinib liposomal formulation for pulmonary hypertension: A QbD approach","volume":"9","author":"Dhoble","year":"2019","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.1096\/fj.201900342RR","article-title":"Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis","volume":"33","author":"Lu","year":"2019","journal-title":"Faseb. J."},{"key":"ref_62","unstructured":"Westerfield, M. (2007). The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish Danio (\u201cBrachydanio Rerio\u201d), University of Oregon."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Khan, M.F., Abutaha, N., Nasr, F.A., Alqahtani, A.S., Noman, O.M., and Wadaan, M.A.M. (2019). Bitter gourd (Momordica charantia) possess developmental toxicity as revealed by screening the seeds and fruit extracts in zebrafish embryos. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2599-0"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/dbio.2002.0711","article-title":"In vivo imaging of embryonic vascular development using transgenic zebrafish","volume":"248","author":"Lawson","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_65","unstructured":"Finney, D.J. (1952). Probit Analysis: A Statistical Treatment of the Sigmoid Response Curve, Cambridge University Press."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/6\/1318\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:06:43Z","timestamp":1760173603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/6\/1318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,13]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["molecules25061318"],"URL":"https:\/\/doi.org\/10.3390\/molecules25061318","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,13]]}}}